Complexity analysis of the visual-motor cross-modalities using the correlation dimension parameter.
This paper focuses on the tremor signal as a window to observe and analyze the central nervous system's functions and organization. In this idea it is proposed a custom system and some methodologies that reveal the cross-modalities influences, specifically, the increased complexity of the neuro-motor system generating the tremor as a result of photic driving activation method. The correlation dimension is used as a measure of system's complexity change and the behaviour of the physiological system is modelled using the Hindmarsh-Rose neuronal model. The proposed system includes: three neurons and their unidirectional coupling - considered to be a possible way the system changes its complexity -, the dynamical noise and the photic driving action. The correlation dimension (CD) analysis was performed on the real tremor signal and on the output signal of the modelled system. The global behaviour of the CD parameter proved to be similar in both cases. Thus, the results are promoting the idea of a complex and structured system that is accounting for the photing driving induced tremor.


ADENOID CYSTIC CARCINOMA MISINTERPRETED AS ANTROCHOANAL POLYP: A RARE PRESENTATION.
Adenoid cystic Carcnoma (ACC) is an uncommon malignant tumour accounting for <1% of all oral and maxillofacial tumors. However, in the sinonasal tract, ACC is the most common salivary gland tumor. The sinonasal ACC is asymptomatic initially or causes non-specific symptoms that are similar to those caused by inflammatory sinus disease and local neurological symptoms such as trigeminal neuralgia in advance stage due to perineural invasion by the tumour.We present a case of 35-year-old female who presented with complaints of nasal obstruction and headache. CT scans revealed an antrochoanal polyp without any bony involvement. The histopathological examination revealed unremarkable respiratory epithelium with underlying sheets and acini of small hyperchromatic cells with hyaline-like material in the lumina, confirming adenoid cystic carcinoma. The highlight of this case is that sinonasal polyps are not always inflammatory in origin, these can be neoplastic also.


Dynamic and unique nucleolar microenvironment revealed by fluorescence correlation spectroscopy.
Organization and functions of the nucleolus is maintained by mobilities and interactions of nucleolar factors. Because the nucleolus is a densely packed structure, molecular crowding effects determined by the molecular concentrations and mobilities in the nucleolus should also be important for regulating nucleolar organization and functions. However, such molecular property of nucleolar organization is not fully understood. To understand the biophysical property of nucleolar organization, the diffusional behaviors of inert green fluorescent protein (GFP) oligomers with or without nuclear localization signals (NLSs) were analyzed under various conditions by fluorescence correlation spectroscopy. Our result demonstrates that the mobility of GFPs inside the nucleolus and the nucleoplasm can be represented by single free diffusion under normal conditions, even though the mobility in the nucleolus is considerably slower than that in the chromatin region. Moreover, the free diffusion of GFPs is found to be significantly size- and NLS-dependent only in the nucleolus. Interestingly, the mobility in the nucleolus is highly sensitive to ATP depletion, as well as actinomycin D (ActD) treatment. In contrast, the ultra-structure of the nucleolus was not significantly changed by ATP depletion but was changed by ActD treatment. These results suggest that the nucleolus behaves similarly to an open aqueous-phase medium with an increased molecular crowding effect that depends on both energy and transcription.


Dravet Syndrome: Diagnosis and Long-Term Course.
Dravet syndrome is one of the most severe epilepsy syndromes of early childhood, and it comes with very high morbidity and mortality. The typical presentation is characterized by hemiclonic or generalized clonic seizures triggered by fever during the first year of life, followed by myoclonic, absence, focal and generalized tonic-clonic seizures. Non-convulsive status epilepticus and epileptic encephalopathy are common. Development is normal in the first year of life, but most individuals eventually suffer from intellectual impairment. Dravet syndrome is associated with mutations in the sodium channel alpha1 subunit gene (SCN1A) in 70-80% of individuals. SCN1A mutation results in inhibition of the GABAergic inhibitory interneurons, leading to excessive neuronal excitation. The "interneuron hypothesis" is the current most accepted pathophysiological mechanism of Dravet syndrome. The mortality rate is increased significantly in Dravet syndrome. Ataxia, a characteristic crouched gait and Parkinson's symptoms may develop in some individuals. It is likely that Dravet syndrome is underdiagnosed in adults with treatment-resistant epilepsy. Early diagnosis is important to avoid anti-seizure medications that exacerbate seizures.


Introduced cryptic species of parasites exhibit different invasion pathways.
Sometimes infectious agents invade and become established in new geographic regions. Others may be introduced yet never become established because of the absence of suitable hosts in the new region. This phenomenon may be particularly true for the many parasites with complex life cycles, where various life stages require different host species. Homogenization of the world's biota through human-mediated invasions may reunite hosts and parasites, resulting in disease outbreaks in novel regions. Here we use molecular genetics to differentiate invasion pathways for two digenean trematode parasites and their exotic host, the Asian mud snail, Batillaria attramentaria. All of the snail haplotypes found in introduced populations in North America were identical to haplotypes common in the areas of Japan that provided oysters for cultivation in North America, supporting the hypothesis that the snails were introduced from Japan with seed oysters. Two cryptic trematode species were introduced to North American populations in high frequencies. We found a marked reduction of genetic variation in one of these species, suggesting it experienced a bottleneck or founder event comparable to that of the host snail. In contrast, no genetic variation was lost in the other parasite species. We hypothesize that this parasite was and is dispersed naturally by migratory shorebirds and was able to establish only after the host snail, B. attramentaria, was introduced to North America. Evaluation of the nature of invasion pathways and postinvasion consequences will aid mitigation of spreading diseases of humans, livestock, and wildlife in an increasingly globalized world.


An autoclave treatment reduces the solubility and antigenicity of an allergenic protein found in buckwheat flour.
The effects of an autoclave treatment of buckwheat flour on a 24-kDa allergenic protein were investigated by measuring reduction in solubility and antibody binding. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that the intensity of the major bands, including that of the 24-kDa allergen, was reduced by the autoclave treatment. The protein solubility in buckwheat flour was variably decreased by the autoclave treatment. Enzyme-linked immunosorbent assay analysis using a monoclonal antibody specific for buckwheat 24-kDa protein showed that the reactivity of protein extracts (10 μg/ml) from buckwheat flour was lowered by the autoclave treatment. The autoclave treatment may reduce the major allergen content of buckwheat. Future studies will determine if autoclaving treatments affect the allergenicity of the 24-kDa buckwheat protein.


Prevention of postoperative osteopenia using IV pamidronate: a pilot study.
Postoperative bone mineral density (BMD) loss, especially after cast immobilization and/or non-weight-bearing, is a well-known phenomenon in children that can cause fracture. Children with marginal bone density are at greatest risk. This prospective randomized control trial compared the effect of single-dose intravenous (IV) pamidronate versus placebo to prevent postoperative BMD loss. Children between the ages of 4 and 18 were included in the study; inclusion criteria included a predisposition to low bone density and hip or lower extremity surgery that would require cast immobilization or non-weight-bearing for at least 4 weeks. Dual-energy x-ray absorptiometry (DXA) scans of the lumbar spine and bilateral distal femora were performed preoperatively and at least 4 weeks postoperatively. Subjects were randomized to receive either a single, low dose of IV pamidronate (1 mg/kg) or placebo, given during the immediate postoperative period. Changes in the BMD were compared using the Mann-Whitney test for significance in the lumbar spine. A multivariate general linear model was used to compare the effect of surgery, DXA region, and treatment on BMD. A total of 24 subjects were included in the study, and 20 completed the protocol. Pamidronate-treated subjects showed a statistically significant difference with a median gain in BMD of 0.029 gm/cm in the lumbar spine compared with the control group, which showed a median loss of 0.025 gm/cm. Treatment did not have a statistically significant effect on BMD loss in the distal femur but trended toward decreased BMD loss (treatment=0.0331 gm/cm, control=0.0416 gm/cm). There were no complications or adverse reactions. This small pilot study shows that single-dose postoperative pamidronate mitigated postoperative BMD loss in at-risk children, which may in turn decrease postoperative fracture risk. Further investigation into the use of IV pamidronate in postoperative patients is warranted. Level 1 double-blinded randomized control trial.


Anxiety levels of patients undergoing common dermatologic procedures versus those seeking general dermatologic care.
Patients undergoing Mohs micrographic surgery frequently experience anxiety as a result of multiple potential factors. There is currently no data regarding how this anxiety compares to other common procedures performed in dermatology offices, such as shave biopsy and excision, relative to a general dermatology visit. Herein, we conducted a survey of 471 dermatology patients at an academic medical center, using a validated tool (Visual Analogue Scale from 1 "no anxiety at all" to 10 "extremely anxious").


Multiscale self-calibrated pulmonary nodule detection network fusing dual attention mechanism.
Objective. In this study, we propose a model called DEPMSCNet (a multiscale self-calibration network) that has a high sensitivity and low false positive rate for detecting pulmonary nodules.Approach. First, at the feature extraction stage, we propose to use the REPSA-MSC module instead of the traditional convolutional neural network. The module extracts multiscale information from the feature map based on the image pyramid strategy while introducing adaptive convolutional branches to detect contextual information at each position of the multiscale, thereby expanding the receptive field and improving sensitivity. At the same time, multiple branches are adaptively weighted by channel attention, and the weights of different branches are adjusted to better generate pixel-level attention. Secondly, the proposed DSAM (dual-path spatial attention module) operates at the information fusion stage. This module fully exploits the rich spatial information of CT scans, obtains receptive field information from two branches, combines low-level feature map information with high-level semantic information, and enhances location-related information to effectively improve specificity. Thirdly, the focal loss function is used to solve the problem of positive and negative sample imbalance.Mainresults. The proposed model has been evaluated on the public lung nodule analysis (LUNA16) challenge dataset. The technique outperforms the most recent state-of-the-art detection algorithms in terms of sensitivity and specificity, obtaining a sensitivity of 0.988 and a competitive performance metric (CPM) of 0.963.Significance. Ablation experiments show that the two modules proposed in this paper effectively reduce false positives and improve sensitivity. This model effectively reduces the number of false positive nodules that doctors see on CT scans.


Chemical properties of the leinamycin-guanine adduct in DNA.
The reaction of the antitumor agent leinamycin with thiols converts this natural product into an episulfonium ion that alkylates the N7-position of guanine residues in double-stranded DNA. It is reported here that depurination of this adduct is unusually facile, occurring with a half-life of about 3.5 h at pH 7 and 37 degrees C in duplex DNA. This is one of the most rapid depurination reactions ever observed for an N7-alkylguanine residue. The rate constant for the depurination reaction was measured at several temperatures, and the activation parameters were calculated from the data. The energy of activation (E(a)) for this reaction is 24.6 kcal/mol, and the Arrhenius A value is 1.2 x 10(13) s(-1). These values correspond to a DeltaH(++) = 24.0 kcal/mol and DeltaS(++) = -0.78 eu and are consistent with the expected unimolecular (D(N) + A(N)) mechanism for the depurination reaction. Changes in ionic strength (0-500 mM NaCl) or pH (3-8) do not significantly alter the rate of depurination, and the base excision repair protein Aag, which removes a variety of N7-alkylguanine residues from duplex DNA, does not excise the leinamycin-guanine adduct. Possible biological implications of this rapid depurination process are considered. Finally, during the course of these studies, the release of hydrolyzed leinamycin (4; Scheme 1) from leinamycin-modified DNA was observed. This result suggests that leinamycin may be a reversible DNA alkylating agent.


Characterization of high-level aminoglycoside-resistant enterococci in Kuwait hospitals.
This study investigated the distribution of genes for aminoglycoside-modifying enzymes (AME) and the genetic relatedness of high-level aminoglycoside-resistant enterococci isolated in Kuwait hospitals. A total of 117 enterococci, consisting of 109 Enterococcus faecalis, seven Enterococcus faecium, and one Enterococcus casseliflavus were studied. The MICs of gentamicin, kanamycin, amikacin, tobramycin, and streptomycin were determined by agar dilution and the genes encoding the AAC(6')- APH(2"), ANT(4'), APH(3'), APH (2")-Ib, APH (2")-Ic, APH (2")-Id, and ANT(6) enzymes were amplified by PCR. They were typed by pulsed-field gel electrophoresis (PFGE). Filter mating was used to transfer gentamicin resistance determinants. They were all resistant to kanamycin (MIC 2000 mg/L). Fifty-five isolates were resistant to gentamicin (MIC 500 mg/L), 72 were resistant to tobramycin (MIC 64 mg/L), 115 were resistant to amikacin (MIC 64 mg/L), and 97 were resistant to streptomycin (MIC 1000 mg/L). The aac(6')-Ie-aph(2")-Ia was detected in all isolates with gentamicin MIC 500 mg/L and in 15 isolates with gentamicin MIC 256 mg/L. The aph(3')-IIIa gene was detected in 101 isolates, whereas the ant(6')-Ia gene was detected in 85 of the 97 streptomycin-resistant isolates with MIC 1000 mg/L. The aac(6')-Ii gene was detected only in the seven E. faecium isolates. None of them contained ant(4')-Ia, aph(2")-Ib, aph(2")-Ic and aph(2")-Id. PFGE revealed heterogeneous patterns with no dominant clone. The results demonstrated that AME are common in aminoglycoside-resistant enterococci isolated in Kuwait. However, the absence of a dominant clone suggests that they acquired high-level aminoglycoside independently.


Bias analysis and the simulation-extrapolation method for survival data with covariate measurement error under parametric proportional odds models.
It has been well known that ignoring measurement error may result in substantially biased estimates in many contexts including linear and nonlinear regressions. For survival data with measurement error in covariates, there has been extensive discussion in the literature with the focus on proportional hazards (PH) models. Recently, research interest has extended to accelerated failure time (AFT) and additive hazards (AH) models. However, the impact of measurement error on other models, such as the proportional odds model, has received relatively little attention, although these models are important alternatives when PH, AFT, or AH models are not appropriate to fit data. In this paper, we investigate this important problem and study the bias induced by the naive approach of ignoring covariate measurement error. To adjust for the induced bias, we describe the simulation-extrapolation method. The proposed method enjoys a number of appealing features. Its implementation is straightforward and can be accomplished with minor modifications of existing software. More importantly, the proposed method does not require modeling the covariate process, which is quite attractive in practice. As the precise values of error-prone covariates are often not observable, any modeling assumption on such covariates has the risk of model misspecification, hence yielding invalid inferences if this happens. The proposed method is carefully assessed both theoretically and empirically. Theoretically, we establish the asymptotic normality for resulting estimators. Numerically, simulation studies are carried out to evaluate the performance of the estimators as well as the impact of ignoring measurement error, along with an application to a data set arising from the Busselton Health Study. Sensitivity of the proposed method to misspecification of the error model is studied as well.


A polymorphic gene nested within an intron of the tau gene: implications for Alzheimer's disease.
A previously undescribed gene, Saitohin (STH), has been discovered in the intron between exons 9 and 10 of the human tau gene. STH is an intronless gene that encodes a 128-aa protein with no clear homologs. The tissue expression of STH is similar to tau, a gene that is implicated in many neurodegenerative disorders. In humans, a single nucleotide polymorphism that results in an amino acid change (Q7R) has been identified in STH and was used in a case control study. The Q7R polymorphism appears to be over-represented in the homozygous state in late onset Alzheimer's disease subjects.


Mesoporous Silica Nanoparticles Loaded with Cisplatin and Phthalocyanine for Combination Chemotherapy and Photodynamic Therapy in vitro.
Mesoporous silica nanoparticles (MSNs) have been synthesized and loaded with both aluminum chloride phthalocyanine (AlClPc) and cisplatin as combinatorial therapeutics for treating cancer. The structural and photophysical properties of the MSN materials were characterized by different spectroscopic and microscopic techniques. Intracellular uptake and cytotoxicity were evaluated in human cervical cancer (HeLa) cells by confocal laser scanning microscopy (CLSM) and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays, respectively. The CLSM experiments showed that the MSN materials can be readily internalized in HeLa cells. The cytotoxic experiments demonstrated that, after light exposure, the combination of both AlClPc and cisplatin compounds in the same MSN platform potentiate the toxic effect against HeLa cells in comparison to the control AlClPc-MSN and cisplatin-MSN materials. These results show the potential of using MSN platforms as nanocarriers for combination photodynamic and chemotherapies to treat cancer.


Outcomes of endovascular thrombectomy with and without bridging thrombolysis for acute large vessel occlusion ischaemic stroke.
Endovascular thrombectomy (EVT) for management of large vessel occlusion (LVO) acute ischaemic stroke is now current best practice. To determine if bridging intravenous (i.v.) alteplase therapy confers any clinical benefit. A retrospective study of patients treated with EVT for LVO was performed. Outcomes were compared between patients receiving thrombolysis and EVT with EVT alone. Primary end-points were reperfusion rate, 90-day functional outcome and mortality using the modified Rankin Scale (mRS) and symptomatic intracranial haemorrhage (sICH). A total of 355 patients who underwent EVT was included: 210 with thrombolysis (59%) and 145 without (41%). The reperfusion rate was higher in the group receiving i.v. tissue plasminogen activator (tPA) (unadjusted odds ratio (OR) 2.2, 95% confidence interval (CI): 1.29-3.73, P = 0.004), although this effect was attenuated when all variables were considered (adjusted OR (AOR) 1.22, 95% CI: 0.60-2.5, P = 0.580). The percentage achieving functional independence (mRS 0-2) at 90 days was higher in patients who received bridging i.v. tPA (AOR 2.17, 95% CI: 1.06-4.44, P = 0.033). There was no significant difference in major complications, including sICH (AOR 1.4, 95% CI: 0.51-3.83, P = 0.512). There was lower 90-day mortality in the bridging i.v. tPA group (AOR 0.79, 95% CI: 0.36-1.74, P = 0.551). Fewer thrombectomy passes (2 versus 3, P = 0.012) were required to achieve successful reperfusion in the i.v. tPA group. Successful reperfusion (modified thrombolysis in cerebral infarction ≥2b) was the strongest predictor for 90-day functional independence (AOR 10.4, 95% CI:3.6-29.7, P < 0.001). Our study supports the current practice of administering i.v. alteplase before endovascular therapy.


Two-step steam pretreatment of softwood with SO2 impregnation for ethanol production.
Two-step steam pretreatment of softwood was investigated with the aim of improving the enzymatic digestibility for ethanol production. In the first step, softwood was impregnated with SO2 and steam pretreated at different severities. The first step was performed at low severity to hydrolyze the hemicellulose and release the sugars into the solution. The combination of time and temperature that yielded the highest amount of hemicellulosic sugars in the solution was determined. In the second step, the washed solid material from the optimized first step was impregnated once more with SO2 and steam pretreated under more severe conditions to enhance the enzymatic digestibility. The investigated temperature range was between 180 and 220 degrees C, and the residence times were 2, 5 and 10 min. The effectiveness of pretreatment was assessed by both enzymatic hydrolysis of the solids and simultaneous saccharification and fermentation (SSF) of the whole slurry after the second pretreatment step, in the presence of antibiotics. For each pretreatment combination, the liquid fraction was fermented to determine any inhibiting effects. At low severity in the second pretreatment step, a high conversion of cellulose was obtained in the enzymatic hydrolysis step, and at a high severity a high conversion of cellulose was obtained in the second pretreatment step. This resulted in an overall yield of sugars that was nearly constant over a wide range of severity. Compared with the one-step steam pretreatment, the two-step steam pretreatment resulted in a higher yield of sugar and in a slightly higher yield of ethanol. The overall sugar yield, when assessed by enzymatic hydrolysis, reached 80%. In the SSF configuration, an overall ethanol yield of 69% was attained.


Genome-wide association study of maize resistance to Pythium aristosporum stalk rot.
Stalk rot, a severe and widespread soil-borne disease in maize, globally reduces yield and quality. Recent documentation reveals that Pythium aristosporum has emerged as one of the dominant causal agents of maize stalk rot. However, a previous study of maize stalk rot disease resistance mechanisms and breeding had mainly focused on other pathogens, neglecting P. aristosporum. To mitigate crop loss, resistance breeding is the most economical and effective strategy against this disease. This study involved characterizing resistance in 295 inbred lines using the drilling inoculation method and genotyping them via sequencing. By combining with population structure, disease resistance phenotype, and genome-wide association study (GWAS), we identified 39 significant single-nucleotide polymorphisms (SNPs) associated with P. aristosporum stalk rot resistance by utilizing six statistical methods. Bioinformatics analysis of these SNPs revealed 69 potential resistance genes, among which Zm00001d051313 was finally evaluated for its roles in host defense response to P. aristosporum infection. Through virus-induced gene silencing (VIGS) verification and physiological index determination, we found that transient silencing of Zm00001d051313 promoted P. aristosporum infection, indicating a positive regulatory role of this gene in maize's antifungal defense mechanism. Therefore, these findings will help advance our current understanding of the underlying mechanisms of maize defense to Pythium stalk rot.


[Penetration of cervical mucus by native and cryopreserved sperm--the Kremer test].
The penetration of native and cryopreserved human spermatozoa into cervical mucus--the Kremer's test. Retrospective study. Department of Obstetrics and Gynaecology, Medical Faculty, Charles University and Faculty Hospital, Plzen. Human cervical mucus was collected from 73 women visiting the Division of immunology of reproduction, Department of Obstetrics and Gynaecology in Plzen. Native spermatozoa was obtained from the patients of the Division of Immunology of Reproduction as well. Cryopreserved only in its seminal plasma was obtained from the spermabank of our department. The distance of penetration in centimetres from the start was examined in inverse microscopy after 30, 60, 90 and 90 minutes. Also the character and duration of the sperm motility was analyzed. The penetration of native spermatozoa was higher than the penetration of cryopreserved spermatozoa in each case. The native spermatozoa had a higher penetrability, motility and life-ability. Spermatozoa preserved only in its seminal plasma had the parameters demonstrably lower. Nevertheless these spermatozoa can be successfully used for homologue or heterologue insemination or for IVF because these spermatozoa do not loose its enzymatic and remaining energetic equipment by penetration the cervical canal. The Kremer's test belongs to the reliable methods of penetration ability of native and cryopreserved sperms.


Near-total gluteal defect reconstruction with bilateral delayed giant lumbar artery perforator flaps: A case report.
The reconstruction of the near-total or total gluteal defects is challenging. Reconstructive options were restricted when the gluteal flaps were sacrificed. The lumbar artery perforator flap (LAPF) has been recently popularized as an alternative option for sacral and gluteal pressure ulcers. Extension of flap size may be needed in extensive defects. We aim to use the delay phenomenon to increase lumbar artery perforator flap territory to reconstruct near total gluteal defect. A 36-year-old woman was referred to our clinic with defect sizes of 23 × 23 cm and 25 × 17 cm for the right and left gluteal regions. She had a history of multiple surgeries for her paraplegia-related sacrogluteal pressure sores. The reconstruction was started on the left side with delaying incisions to the flap borders. Seven days later, the left gluteal defect was reconstructed with 27 × 19 cm LAPF based on a second lumbar artery perforator. At the same session, the delaying incision was performed to the borders of the right LAPF. On day 14, the right gluteal defect was closed with a 25 × 25 cm-sized right LAPF. No flap loss and early complications were seen. The patient was discharged without complication after 10 days after the last operation. The patient was followed up for 1 year. A right ischial pressure ulcer due to wheelchair use was encountered, which was managed with conservative wound care in the 8th month. Giant-sized lumbar artery perforator flaps may be obtained by delay phenomenon to reconstruct near-total or total gluteal pressure sores.


Characterization of the achromobactin iron acquisition operon in Sodalis glossinidius.
Sodalis glossinidius is a facultative, extra- and intracellular symbiont found in most tissues of the tsetse fly (Glossinia sp.). Sodalis has a putative achromobactin siderophore iron acquisition system on the pSG1 plasmid. Reverse transcription (RT)-PCR analysis revealed that the achromobactin operon is transcribed as a single polycistronic molecule and is expressed when Sodalis is within the tsetse fly. Expression of the achromobactin operon was repressed under iron-replete conditions; in a mutant that lacks the iron-responsive transcriptional repressor protein Fur, expression was aberrantly derepressed under these iron-replete conditions, indicating that the Fur protein repressed achromobactin gene expression when iron was plentiful. A putative Fur binding site within the Sodalis achromobactin promoter bound Fur in Escherichia coli Fur titration assays. Wild-type Sodalis produced detectable siderophore in vitro, but a mutation in the putative achromobactin biosynthesis gene acsD eliminated detectable siderophore production in Sodalis. Reduced growth of the siderophore synthesis mutant was reconstituted by addition of exogenous achromobactin, suggesting the strain retains a functional siderophore transport system; however, reduced growth of a Sodalis ferric-siderophore outer membrane receptor mutant with a mutation in acr was not reconstituted by exogenous siderophore due to its defective transporter. The Sodalis siderophore synthesis mutant showed reduced growth in tsetse that lacked endogenous symbionts (aposymbiotic) when the flies were inoculated with Sodalis intrathoracically, but not when inoculated per os. Our findings suggest that Sodalis siderophores play a role in iron acquisition in certain tsetse fly tissues and provide evidence for the regulation of iron acquisition mechanisms in insect symbionts.


GPS-identified, low-level nocturnal activity of vervets (Chlorocebus pygerythrus) and olive baboons (Papio anubis) in Laikipia, Kenya.
Except for owl monkeys (Aotus spp.), all anthropoid primates are considered strictly diurnal. Recent studies leveraging new technologies have shown, however, that some diurnal anthropoids also engage in nocturnal activity. Here we examine the extent to which vervets (Chlorocebus pygerythrus) and olive baboons (Papio anubis) are active at night. We deployed GPS collars with tri-axial accelerometer data loggers on 18 free-ranging adult females: 12 vervets spread among 5 social groups, and 6 olive baboons spread among 4 groups. Their locations were recorded every 15 min, and their activity levels, for 3 s/min over 7.5 months. We also used camera traps that were triggered by heat and movement at seven sleeping sites. Travel was detected on 0.4% of 2,029 vervet-nights involving 3 vervets and 1.1% of 1,109 baboon-nights involving 5 baboons. Travel was mainly arboreal for vervets but mainly terrestrial for baboons. During the night, vervets and baboons were active 13% and 15% of the time, respectively. Activity varied little throughout the night and appeared unaffected by moon phase. Our results confirm the low nocturnality of vervets and olive baboons, which we suggest is related to living near the equator with consistent 12-hr days, in contrast to other anthropoids that are more active at night. Since anthropoid primates are thought to have evolved in northern latitudes, with later dispersal to tropical latitudes, our results may have implications for understanding the evolution of anthropoid diurnality.


Planar carbon radical's assembly and stabilization, a way to design spin-based molecular materials.
In this work, we report the first computational study on the assembly and stabilization of a novel kind of radical, i.e., the planar tetracoordinate carbon radical CAl(4)(-). Based on the 6-31+G(d)-UB3LYP, UMP2 and UCCSD(T) calculations on charged [D(CAl(4))M](q-), saturated [D(CAl(4))M(n)] and extended (CpM)(p)(CAl(4))(q) sandwich-like compounds (D = CAl(4)(-), Cp(-); M = Li, Na, K, Be, Mg, Ca), we find that for the six metals, the planar radical CAl(4)(-) can only be assembled in the "hetero-decked sandwich" scheme (e.g. [CpM(CAl(4))](q-)) rather than the traditional "homo-decked sandwich" scheme. Moreover, the low and high spin states of the designed sandwich-like species are perfectly degenerate during assembly. This can be ascribed to the good spin conservation of the CAl(4)(-) deck and the good spatial separation between two CAl(4)(-) decks. Our results show for the first time that the planar radical CAl(4)(-) can act as a new type of spin-embedded "superatom" for cluster assembly when it is assisted by a rigid partner like Cp(-). The good spin-conservation of CAl(4)(-) is very promising for the future design of novel paramagnetic and diamagnetic materials. The ionic, clustering and radical interactions between the two decks are analyzed in detail, which is quite crucial to improve the insight and understanding of the nature and origin of the interactions of the "deck-core-deck" in the metallocenes. Such information is also important in understanding the radical reactions and designing novel spin-based molecular materials. The present study should be expected to enrich the flat carbon chemistry, radical chemistry, metallocene chemistry and combinatorial chemistry.


Two new species of the Clubiona corticalis-group from Guizhou Province, China (Araneae: Clubionidae).
Clubiona Latreille, 1804, the largest genus in family Clubionidae, currently includes 495 species worldwide with 126 species from China (Li Lin 2016; World Spider Catalog 2018). Due to the high diversity in Clubiona, several subgenera and species-groups have been proposed (Wang et al. 2015). While there is no agreement on the limits of most species-groups of Clubiona (Deeleman-Reinhold 2001), the corticalis-group has been widely considered as putatively monophyletic. The group presents a distinct set of characters (Mikhailov 1995; Deeleman-Reinhold 2001; Liu et al. 2016) and the species composition of the core-group is relatively stable (Mikhailov 1995; Deeleman-Reinhold 2001; Dankittipakul Singtripop 2008; Wu et al. 2015). At least two generic names are available for the corticalis-group, Atalia Thorell, 1887 and Paraclubiona Lohmander, 1944 (Mikhailov 2012). Spiders of the corticalis-group are well studied in China and several new species have been described in recent years (Yu et al. 2012; Zhu et al. 2012; Wang et al. 2015; Wu et al. 2015; Liu et al. 2016; He et al. 2016). Up to now, the Clubiona corticalis-group has more than 28 Chinese species (Wang et al. 2015; Wu et al. 2015; Liu et al. 2016; He et al. 2016; Yu et al. 2017), making it one of the most well known clubionid groups in China. While examining spiders collected from Guizhou Province, China, we came across some specimens from the Clubiona corticalis-group, which are described here as belonging to two new species.


Robust angle-independent blood velocity estimation based on dual-angle plane wave imaging.
Two-dimensional blood velocity estimation has shown potential to solve the angle-dependency of conventional ultrasound flow imaging. Clutter filtering, however, remains a major challenge for large beam-to-flow angles, leading to signal drop-outs and corrupted velocity estimates. This work presents and evaluates a compounding speckle tracking (ST) algorithm to obtain robust angle-independent 2-D blood velocity estimates for all beam-to-flow angles. A dual-angle plane wave imaging setup with full parallel receive beamforming is utilized to achieve high-frame-rate speckle tracking estimates from two scan angles, which may be compounded to obtain velocity estimates of increased robustness. The acquisition also allows direct comparison with vector Doppler (VD) imaging. Absolute velocity bias and root-mean-square (RMS) error of the compounding ST estimations were investigated using simulations of a rotating flow phantom with low velocities ranging from 0 to 20 cm/s. In a challenging region where the estimates were influenced by clutter filtering, the bias and RMS error for the compounding ST estimates were 11% and 2 cm/s, a significant reduction compared with conventional single-angle ST (22% and 4 cm/s) and VD (36% and 6 cm/s). The method was also tested in vivo for vascular and neonatal cardiac imaging. In a carotid artery bifurcation, the obtained blood velocity estimates showed that the compounded ST method was less influenced by clutter filtering than conventional ST and VD methods. In the cardiac case, it was observed that ST velocity estimation is more affected by low signal-to-noise (SNR) than VD. However, with sufficient SNR the in vivo results indicated that a more robust angle-independent blood velocity estimator is obtained using compounded speckle tracking compared with conventional ST and VD methods.


Grading of exit sites cannot predict peritonitis in patients on CAPD.
Grading of exit sites was performed at 265 routine outpatient visits of 28 patients starting CAPD between January 1988 and February 1990, with a total observation time of 398.5 months to December 1990. Six patients had no peritonitis episode. The remaining 22 patients suffered from 43 peritonitis episodes. Fifty-eight per cent of these were caused by Staphylococcus epidermidis. Eighty-six per cent of the examinations of exit sites of patients with peritonitis episodes showed 0 to 1 point on an arbitrary grading scale of up to 9 points. Staphylococcus aureus was found after bacterial culture from exit site smears in 3 cases. All were adequately treated. None of these cases showed any peritonitis episodes with this bacteria. No relationship could be found between the grading of the exit site at routine outpatient clinic visits and the appearance of a peritonitis episode. Grading of exit sites is of clinical importance but cannot predict the appearance of peritonitis.


Genistein, an inhibitor of protein tyrosine kinase, is also a competitive antagonist for P1-purinergic (adenosine) receptor in FRTL-5 thyroid cells.
Genistein, a potent inhibitor for protein tyrosine kinase, remarkably inhibited the stimulatory action of N6-(L-2-phenylisopropyl)adenosine (PIA), an A1-adenosine receptor agonist, on thyrotropin (TSH)-induced phospholipase C activation in FRTL-5 thyroid cells. This drug also suppressed both the A1-receptor-mediated inhibition of cAMP accumulation in the cells and binding of [3H]8-cyclopentyl-1,3-dipropylxanthine, a specific antagonist for A1-receptor, to the cell membranes in a competitive manner. Adenosine-induced cAMP accumulation through A2-receptor in pertussis toxin-treated cells was also competitively antagonized by genistein. We conclude that genistein is also a competitive antagonist for P1-purinergic receptors.


Mind-body interventions: applications and potential opportunities for health education practice.
Mind-body interventions (MBIs) have become increasingly popular. In the current article, we examine the potential role of MBIs for improving health and promoting wellness. We first describe typologies of MBIs and prevalence of their use. We also examine the efficacy evidence about how MBIs offer many psychological and physiological benefits, including reductions in disease symptoms and improvements in coping, behavior regulations, quality of life, and well-being. We further discuss how the health education discipline has long supported the inherent holism of the human being, the importance of healing potential of the mind on one's health, and values capacity for self-regulation and describe the potential opportunities for health educators as it relates to MBIs. Finally, we discuss implications for the profession of health education and promotion.


Validation of an automated screening method for persistent organic contaminants in fats and oils by GC×GC-ToFMS.
An screening method, comprised of straightforward sample treatment based on silica clean-up, GC×GC-ToFMS detection and automated data processing with the non-proprietary free downloadable software MetAlignID, has been successfully validated with respect to false negatives for the sum PCB 28, 52, 101, 138, 153 and 180), for the sum of BDE 28, 47, 99, 100, 153, 154 and 183, for the four markers of PAHs and for a number of emerging brominated flame retardants. A screening detection limit (SDL) equal to or lower than the maximum regulatory level was always achieved. MetAlignID considerably decreased the time needed for data treatment from 20 to 5min/file. Automated identification of the signature mass spectral patterns was applied to identify chlorinated- and brominated-containing substances with more than two halogen atoms, and PAH derivates. Although the success rate was variable and needs to be further improved, the tool was considered to be of added value.


Improved overall survival of elderly patients on peritoneal dialysis.
Clinical complications and outcome of 50 patients, age 65 or older, on dialysis during 1985-1990 were studied. There were three groups: Peritoneal Dialysis (PD-10 pts.), Hemodialysis (HD-28 pts.), and both for at least one month each (PD-HD 12 pts.) (8 HD to PD and 4 PD to HD). Analysis included sex, age, bacteremia associated to acute vascular accesses (AVA), peritonitis (PD), other illnesses, hospital days, blood chemistries, quality of life (active, sedentary or bedridden). The most frequent causes of death were septicemia and cardiac failure. No difference was found in age, chemistries, hemoglobin, illnesses or quality of life. The results showed a significant improved overall survival for those in the PD group (77.8%, p less than 0.05) as compared to HD or PD-HD group. Therefore, more emphasis should be placed on using PD for elderly patients.


Surgical treatment of acquired flatfoot deformity: what is the state of practice among academic foot and ankle surgeons in 2002?
This study was performed to review the present approach to the surgical treatment of acquired flatfoot deformity among a cross section of academic foot and ankle surgeons in the United States. A typical case of stage II posterior tibial tendon dysfunction was developed. The hypothetical patient was a healthy 62-year-old male with a symptomatic acquired flatfoot deformity with posterior tibial tendon dysfunction. Nonoperative management had failed. A series of academic foot ankle surgeons were surveyed to identify their proposed operative treatment. Each surgeon surveyed was affiliated with an orthopaedic residency program and was directly responsible for teaching orthopaedic residents. Each surgeon had foot and ankle patients as the major component of their practice. The overall response rate was 81% (104/128). Ninety-seven percent (101/104) of respondents reported that they would employ some type of bony procedure in their surgical treatment. Eighty-eight percent (89/104) described techniques that would preserve the subtalar and talonavicular joints. These included a medializing calcaneal osteotomy in 73% (76/104), a lateral column lengthening in 41% (43/104), and a medial column stabilization (first tarsometatarsal and/or navicular cuneiform arthrodesis) in 15% (16/104). Twelve percent (12/104) reported that they would perform an arthrodesis of one or more of the hindfoot joints. Ninety-eight percent (102/104) of respondents reported that they would employ some type of soft-tissue procedure. Ninety-four percent (98/104) would augment the posterior tibial tendon, 53% (55/104) would formally repair the spring ligament, and 70% (73/104) would address a presumed equinus contracture. There is a wide variation in the approach to surgical treatment of stage II acquired adult flatfoot deformity among academic foot and ankle surgeons. Most surgeons employed a combination of bony and soft-tissue procedures that preserved the subtalar and talonavicular joints.


Identification of biomarkers associated with immune scores in diabetic retinopathy.
Diabetic retinopathy (DR) causes irreversible visual impairment in diabetes mellitus (DM) patients. Immunity played a crucial role in DR. Nevertheless, the triggering mechanism of DR was not yet thorough enough. Herein, we aim to identify the immune-associated genes as biomarkers associated with immune scores that can distinguish early DR from DM without DR. In this study, total RNA of peripheral blood mononuclear cell (PBMC) samples from 15 non-proliferative DR patients and 15 DM patients without DR were collected and the transcriptome sequencing data were extracted. Firstly, the target genes were obtained by intersecting the differentially expressed genes (DEGs), which were screened by "limma", and the module genes (related to immune scores), which were screened by "WGCNA". In order to screen for the crucial genes, three machine learning algorithms were implemented, and a receiver operating characteristic (ROC) curve was used to obtain the diagnostic genes. Moreover, the gene set enrichment analysis (GSEA) was performed to understand the function of diagnostic genes, and analysis of the proportions of immune cells and their association with diagnostic genes was performed to analyze the pathogenesis of DR. Furthermore, the regulatory network of TF-mRNA-miRNA was built to reveal the possible regulation of diagnostic genes. Finally, the quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the mRNA level of diagnostic genes. A total of three immune-associated diagnostic genes, namely, FAM209B, POM121L1P, and PTGES, were obtained, and their expression was increased in PBMC samples of DR, and qRT-PCR results confirmed these results. Moreover, the functions of these genes were associated with immune response. The expression of POM121L1P and PTGES was significantly negatively associated with naive B cells, and the expression of FAM209B was significantly negatively associated with immature dendritic cells. Moreover, ESR1 could regulate both FAM209B and PTGES. This study identified three immune-associated diagnostic genes, FAM209B, POM121L1P, and PTGES, as biomarkers associated with immune scores in DR for the first time. This finding might proffer a novel perspective of the triggering mechanism of DR, and help to understand the role of immune-associated genes in the molecular mechanism of DR more deeply.


Utilization of immobilized archaeal chaperonin for enzyme stabilization.
CpkA and CpkB are thermostable chaperonins from hyperthermophilic archaeon Thermococcus kodakaraensis KOD1. CpkA or CpkB was immobilized onto agarose beads by the carbodiimide coupling method. In order to investigate whether immobilized CpkA or CpkB stabilizes a foreign enzyme, their ability to stabilize enzyme was examined using beta-D-galactosidase from Escherichia coli as a model target. In the absence of chaperonin beads, 38.1% of the total soluble protein was precipitated by heat treatment at 53 degrees C for 30 min. The protein structure of the residual soluble fraction was examined by circular dichroism, indicating that beta-D-galactosidase exists as a mixture of the active folded form and the inactive unfolded form. The specific activity of the residual soluble fraction decreased to 85.1% that of the unheated level (from 149.0 U/mg to 127.0 U/mg), indicating that the active folded form in the heated soluble fraction was 85.2%. In the presence of CpkA- or CpkB-beads, 28.6% or 34.3% of beta-d-galactosidase was precipitated by the same heat treatment. However, the specific activity in the soluble fraction was almost maintained (CpkA, from 151.0 U/mg to 140.3 U/mg; CpkB, from 149.0 U/mg to 140.3 U/mg). These results indicated that CpkA- or CpkB-beads are useful for keeping the enzyme active.


Nasal glial heterotopy in childhood: a case report highlighting the morphological and immunohistochemical features.
We present a case of a 5 months old infant who presented with difficulty in breathing and a visible intranasal swelling. Clinical examination revealed a reddish mass medial to the middle turbinate in the left nasal cavity. MRI was done and a provisional diagnosis of nasal glioma was suggested. The mass was surgically excised and sent for histopathology which showed it to be comprising of astrocytes and neuroglial fibers intermixed with a fibrovascular connective tissue stroma. The presence of Glial fibrillary acid protein (GFAP) confirmed the presence of glial tissue.


Small-dose propofol sedation attenuates the formation of reactive oxygen species in tourniquet-induced ischemia-reperfusion injury under spinal anesthesia.
The release of a tourniquet produces reactive oxygen species (ROS), which can cause ischemia-reperfusion injury. We investigated the effects on ROS production in 22 adult ASA physical status I-II patients sedated with small-dose propofol infusion and IV midazolam undergoing elective total knee replacement under intrathecal anesthesia, allocated randomly to one of two groups. In the Propofol group, sedation was performed with propofol 0.2 mg/kg followed by infusion at a rate of 2 mg. kg(-1). h(-1). In the Control group, IV midazolam 5 mg was given. ROS production was measured by lucigenin chemiluminescence analysis. Blood samples were obtained from the radial artery after spinal anesthesia, 1 min before release of the tourniquet and 5 and 20 min after reperfusion. The ischemic time was approximately 70 min. ROS production decreased nonsignificantly before reperfusion in both groups but increased significantly 5 and 20 min after reperfusion in the Midazolam group. In the Propofol group, no significant increase of ROS production was found. We conclude that small-dose propofol infusion attenuates ROS production in tourniquet-induced ischemia-reperfusion injury. Small-dose propofol sedation, compared with IV midazolam, attenuates free radical production after release of the tourniquet during total knee replacement under spinal anesthesia.


T-cell lineage of a Friend virus-induced lymphatic leukemia in athymic rats.
Athymic (rnu/rnu) and euthymic rats inoculated with the Friend virus-associated lymphatic leukemia virus developed lymphocytic leukemia. Neoplastic cells from these animals were evaluated by means of indirect immunofluorescence and flow cytofluorometry with monoclonal antibodies Ox-1, Ox-7, and W3/25, which react with surface antigens present on normal rat lymphoid cell populations. Lymphoid cells from leukemic animals revealed characteristic alterations in cell surface fluorescence profiles when compared to normal, healthy controls. Athymic and euthymic leukemic rats were similar in that many cells from both the spleen and bone marrow had markers on the cell surface normally found on thymocytes but not on mature peripheral lymphocytes. These studies provided evidence supporting the presence of T-lineage lymphocytes in the athymic rat. Further, this population of early or "pre"-T-lymphocytes included the predominant leukemia cell type induced by the Friend virus-associated lymphatic leukemia virus.


Intercellular Adhesion Molecular-5 as Marker in HIV Associated Neurocognitive Disorder.
Despite the use of antiretroviral drugs HIV associated neurocognitive disorders (HAND) are still common in HIV-seropositive patients. Identification of HIV patients with cognitive impairment in early-stage might benefit a great deal from disease progression monitoring and treatment adjustment. Intercellular adhesion molecule-5 (ICAM5), characteristically expressed on neuron, may suppress immune functions by inhibition of T cell activation in central nervous system. Previous studies have shown that ICAM5 could be detected in patients with brain injury. To investigate the relationship between cognitive impairment and ICAM5 in HIV patients, we compared soluble ICAM5 levels in paired CSF and plasma specimens from HIV-infected individuals with or without neurocognitive impairment. sICAM5 concentrations were measured by ICAM5 ELISA kit. A total of 41 Patients were classified into HIV infected with normal cognition (HIV-NC) and impaired cognition groups (HIV-CI) based on Memorial Sloan-Kettering Scale. CSF and plasma levels of sICAM5 in HIV-CI patients were significantly higher than HIV-NC group (p<0.0001, p=0.0054 respectively). sICAM5 concentrations in plasma strongly correlated with sICAM5 in CSF (r=0.7250, p<0.0001) and S100B in CSF (r=0.3812, p<0.0139). Among 6 follow-up patients we found that sICAM5 levels in CSF and plasma might change consistently with HAND progression. In summary, we have shown that the expressions of sICAM5 in CSF and plasma may correlate with neurocognitive impairment in HIV infected patients. The elevation of sICAM5 in plasma were correspond with that in CSF as a consequence of blood-brain barrier permeability changes. ICAM5 can serve as a potential and readily accessible biomarker to predict HIV associated neurocognitive disorder.


Randomized Controlled Trial of Azithromycin versus Doxycycline or Chloramphenicol for Treatment of Uncomplicated Pediatric Scrub Typhus.
To evaluate the efficacy and safety of azithromycinfor treatment of uncomplicated pediatric scrub typhus. A randomized controlled trial was performed. We compared azithromycin with doxycycline or chloramphenicol in uncomplicated pediatric scrub typhus from inpatient pediatric department of Chiangrai Prachanukroh Hospital. The primary outcome was cure rate at day 3. The secondary outcomes were timing to defervescence within 72 hours, side effects, and relapsed rate. We compared data between both groups with Fisher's exact test or Mann-Whitney U test, and failure rate was demonstrated by Kaplan-Meier survival curve and Log-rank test. We included 57 patients, ofwhom, 28 were assigned to doxycycline or chloramphenicol (control group) and 29 to azithromycin (study group). The baseline characteristics of both groups were similar The cure rate was 85.7% in the doxycycline or chloramphenicol group, as compared to 79.3% in the azithromycin group (p = 0.73), and a median time to defervescence was 30 hours (IQR 21, 48) vs. 36 hours (IQR 20, 68) respectively (p = 0.166). There was a little minor side effect in azithromycin group. No relapsed was found in either groups. Azithromycin was as effective as doxycycline or chloramphenicol in treatment of uncomplicated pediatric scrub typhus.


Human papillomavirus type 59 immortalized keratinocytes express late viral proteins and infectious virus after calcium stimulation.
Human papillomavirus type 59 (HPV 59) is an oncogenic type related to HPV 18. HPV 59 was recently propagated in the athymic mouse xenograft system. A continuous keratinocyte cell line infected with HPV 59 was created from a foreskin xenograft grown in an athymic mouse. Cells were cultured beyond passage 50. The cells were highly pleomorphic, containing numerous abnormally shaped nuclei and mitotic figures. HPV 59 sequences were detected in the cells by DNA in situ hybridization in a diffuse nuclear distribution. Southern blots were consistent with an episomal state of HPV 59 DNA at approximately 50 copies per cell. Analysis of the cells using a PCR/reverse blot strip assay, which amplifies a portion of the L1 open reading frame, was strongly positive. Differentiation of cells in monolayers was induced by growth in F medium containing 2 mM calcium chloride for 10 days. Cells were harvested as a single tissue-like sheet, and histologic analysis revealed a four-to-six cell-thick layer. Transcripts encoding involucrin, a cornified envelope protein, and the E1/E4 and E1/E4/L1 viral transcripts were detected after several days of growth in F medium containing 2 mM calcium chloride. The E1/E4 and L1 proteins were detected by immunohistochemical analysis, and virus particles were seen in electron micrographs in a subset of differentiated cells. An extract of differentiated cells was prepared by vigorous sonication and was used to infect foreskin fragments. These fragments were implanted into athymic mice. HPV 59 was detected in the foreskin xenografts removed 4 months later by DNA in situ hybridization and PCR/reverse blot assay. Thus, the complete viral growth cycle, including production on infectious virus, was demonstrated in the HPV 59 immortalized cells grown in a simple culture system.


The armamentarium of treatments for bipolar disorder: a review of the literature.
To assess current pharmacotherapeutic options for bipolar disorder, with particular emphasis on the use of antipsychotic agents, Medline and EMBASE were searched between January 1980 and December 2005 using the keywords "schizoaffective disorder" and "bipolar disorder", combined with various antidepressants, antipsychotics, lithium or other mood stabilizers. English-language articles, review articles and original research articles were reviewed. Most data are available for the "mood stabilizers" lithium and valproate. However, these agents have important limitations regarding their tolerability and efficacy in certain groups. Newer anticonvulsants, especially lamotrigine, have demonstrated efficacy across mood-symptom domains. Antidepressants are not generally favoured as monotherapy in patients with bipolar depression or schizoaffective disorder, due to their potential to induce switching to manic states. However, data are emerging for the efficacy of selective serotonin reuptake inhibitors for bipolar depression in combination with atypical antipsychotics. Atypical antipsychotics may also be used as monotherapy or in conjunction with mood stabilizers for the treatment of acute mania and for continuing maintenance therapy. The choice of antipsychotic may be influenced by the therapeutic situation; formulations that facilitate administration in the acute scenario can provide rapid tranquillization, whereas those that enhance compliance may have a place in maintenance therapy. Our results suggest a growing role for atypical antipsychotics in the treatment of bipolar disorder and further data are anticipated.


Fractalkine is a "find-me" signal released by neurons undergoing ethanol-induced apoptosis.
Apoptotic neurons generated during normal brain development or secondary to pathologic insults are efficiently cleared from the central nervous system. Several soluble factors, including nucleotides, cytokines, and chemokines are released from injured neurons, signaling microglia to find and clear debris. One such chemokine that serves as a neuronal-microglial communication factor is fractalkine, with roles demonstrated in several models of adult neurological disorders. Lacking, however, are studies investigating roles for fractalkine in perinatal brain injury, an important clinical problem with no effective therapies. We used a well-characterized mouse model of ethanol-induced apoptosis to assess the role of fractalkine in neuronal-microglial signaling. Quantification of apoptotic debris in fractalkine-knockout (KO) and CX3CR1-KO mice following ethanol treatment revealed increased apoptotic bodies compared to wild type mice. Ethanol-induced injury led to release of soluble, extracellular fractalkine. The extracellular media harvested from apoptotic brains induces microglial migration in a fractalkine-dependent manner that is prevented by neutralization of fractalkine with a blocking antibody or by deficiency in the receptor, CX3CR1. This suggests fractalkine acts as a "find-me" signal, recruiting microglial processes toward apoptotic cells to promote their clearance. Next, we aimed to determine whether there are downstream alterations in cytokine gene expression due to fractalkine signaling. We examined mRNA expression in fractalkine-KO and CX3CR1-KO mice after alcohol-induced apoptosis and found differences in cytokine production in the brains of these KOs by 6 h after ethanol treatment. Collectively, this suggests that fractalkine acts as a "find me" signal released by apoptotic neurons, and subsequently plays a critical role in modulating both clearance and inflammatory cytokine gene expression after ethanol-induced apoptosis.


Regulation of laryngeal resistance and maximum power transfer with semi-occluded airway vocalization.
Steady airflow resistances in semi-occluded airways as well as acoustic impedances in vocalization are quantified from the lungs to the lips. For clinical and voice training applications, the primary focus is on two airway conditions, an oral semi-occlusion and a semi-occlusion above the vocal folds. Laryngeal airflow resistance is divided into glottal airflow resistance and epilaryngeal airway resistance. Maximum aerodynamic power is transferred to the vocal tract if the glottal airflow resistance is reduced while the epilaryngeal airway resistance is increased. A semi-occlusion at the lips helps to set up this condition. For the acoustic power transfer, the epilaryngeal airway also serves to match the impedance of the source to the impedance of the vocal tract.


Acute edematous pancreatitis impairs pancreatic secretion in rats.
There are few observations of in vivo pancreatic secretory changes that accompany acute pancreatitis. We hypothesized that acute pancreatitis impairs pancreatic exocrine function. We developed a conscious-rat experimental preparation with gastric, duodenal, bile, and pancreatic fistulas. We studied cholecystokinin-stimulated pancreatic secretion in conscious rats before and after inducing acute pancreatitis with supramaximal administration of caerulein--5 micrograms/kg/hr intravenously for 6 hours. Marked hyperamylasemia developed in all rats immediately after administration of caerulein. Basal and cholecystokinin-stimulated pancreatic juice flow and protein (enzyme) secretion decreased significantly 24 hours after acute pancreatitis was induced even though plasma amylase returned to basal levels. We conclude that acute pancreatitis markedly impairs pancreatic secretion.


N-(2-(Diphenylphosphino)ethyl)-2-alkyl-5,6,7,8-tetrahydro-quinolin-8-amines iron(ii) complexes: structural diversity and the ring opening polymerization of ε-caprolactone.
A series of N-(2-(diphenylphosphino)ethyl)-2-alkyl-5,6,7,8-tetrahydroquinolin-8-amines was prepared and used in individually reacting with iron chloride under nitrogen atmosphere to form their iron(ii) complexes Fe1-Fe6. All compounds were characterized using FT-IR spectroscopy and elemental analyses, the organic compounds were confirmed with NMR measurements, and the iron complexes were submitted to single-crystal X-ray diffraction, revealing Fe1, Fe2, Fe4, Fe5, and Fe6 as either mono- or di-nuclear forms. Forming a binary system in situ with two equivalents of LiCH2SiMe3, all iron complexes Fe1-Fe6 efficiently initiated the ring opening polymerization of ε-caprolactone, achieving the TOF up to 8.8 × 103 h-1. More importantly, the resultant polycaprolactone (PCL) possessed high molecular weights with the Mn range of 9.21-24.3 × 104 g mol-1, being a rare case of the iron(ii) catalyst in producing PCL with such high molecular weight. The 1H NMR and MALDI-TOF investigations demonstrated that the PCLs were linear features capped with a methoxy group or CH2SiMe3 or cyclic structure that varied with the molar ratio of [ε-CL]/Fe.


Improving breast self-examination compliance: a Southwest Oncology Group randomized trial of three interventions.
Only 20-40% of U.S. women conduct breast self-examination (BSE). This Southwest Oncology Group experimental study compared the impact of three interventions on BSE compliance. Subjects were randomly assigned to one of three arms: (1) physician message; (2) physician message and BSE class; or (3) physician message, BSE class, and reinforcement (phone and postcard). Compliance (frequency and accuracy) was measured by interview at intake and at 6 months and by phone contact at 1 year. Logistic and multiple regression were employed. This analysis included 2,233 subjects from six institutions. At 1 year the percentages of women doing BSE were 59, 62, and 78% for Arms 1-3, respectively; gains over intake frequency (27% average) were significant within each arm (P < or = 0.0001). At both 6 months and 1 year the differences between Arm 1 and Arm 2 average accuracy scores and the differences between Arm 2 and Arm 3 in the percentage of women doing BSE were significant (P < or = 0.0001). Findings within institutions were consistent with the overall findings. The addition of a BSE class increased accuracy over physician message alone; physician message, BSE class, and reinforcement gave the highest percentage of women doing BSE.


A basal aïstopod from the earliest Pennsylvanian of Canada, and the antiquity of the first limbless tetrapod lineage.
Earliest Pennsylvanian (Bashkirian) vertebrate fossil assemblages of the Joggins Formation (Cumberland Group) of Nova Scotia, Canada, have long been noted for the unique representation of the earliest known crown amniotes, but the overall vertebrate fauna remains poorly understood. The vast majority of Joggins vertebrates have historically been assigned to the Microsauria, a group originally established by Dawson specifically to accommodate the abundant, diminutive fossils of the Joggins Formation. As the Microsauria concept has evolved, some Joggins taxa (e.g. the eureptile Hylonomus lyelli) have been removed from the group, but many of the Joggins 'microsaurs' remain unrevised, obscuring the true diversity of the earliest Pennsylvanian tetrapod fauna. Here we amend part of this problem by revisiting the morphology of Dawson's 'microsaur' Hylerpeton longidentatum. This taxon, represented by the anterior half of a left hemimandible, is here reinterpreted as a plesiomorphic aïstopod and assigned to a new genus, Andersonerpeton. A. longidentatum shows a surprisingly primitive anatomy of the lower jaw, retaining a parasymphyseal fang pair on the dentary, an adsymphyseal bone bearing a denticle field, fangs on all coronoids and parasymphyseal foramina, as well as a prearticular which extends far anterior along the coronoid series. However, several aïstopod characters can also be seen, including a lack of sculpturing on the dentary and a reduced number of recurved, weakly socketed teeth. The anatomy of A. longidentatum corroborates recent phylogenetic work which has placed the origin of aïstopods within the Devonian fin-to-limb transition but preserves a mosaic of characteristics suggesting an even earlier divergence. The presence of an aïstopod in the Joggins fauna expands the taxonomic diversity of the Joggins fauna and suggests that Joggins may preserve a more typical Carboniferous fauna than previously thought.


Surface Enhanced Raman Spectroscopy (SERS) for the Multiplex Detection of Braf, Kras, and Pik3ca Mutations in Plasma of Colorectal Cancer Patients.
In this paper, we discuss the use of a procedure based on polymerase chain reaction (PCR) and surface enhanced Raman spectroscopy (SERS) (PCR-SERS) to detect DNA mutations. Methods: This method was implemented by first amplifying DNA-containing target mutations, then by annealing probes, and finally by applying SERS detection. The obtained SERS spectra were from a mixture of fluorescence tags labeled to complementary sequences on the mutant DNA. Then, the SERS spectra of multiple tags were decomposed to component tag spectra by multiple linear regression (MLR). Results: The detection limit was 10-11 M with a coefficient of determination (R2) of 0.88. To demonstrate the applicability of this process on real samples, the PCR-SERS method was applied on blood plasma taken from 49 colorectal cancer patients to detect six mutations located at the BRAF, KRAS, and PIK3CA genes. The mutation rates obtained by the PCR-SERS method were in concordance with previous research. Fisher's exact test showed that only two detected mutations at BRAF (V600E) and PIK3CA (E542K) were significantly positively correlated with right-sided colon cancer. No other clinical feature such as gender, age, cancer stage, or differentiation was correlated with mutation (V600E at BRAF, G12C, G12D, G12V, G13D at KRAS, and E542K at PIK3CA). Visually, a dendrogram drawn through hierarchical clustering analysis (HCA) supported the results of Fisher's exact test. The clusters drawn by all six mutations did not conform to the distributions of cancer stages, differentiation or cancer positions. However, the cluster drawn by the two mutations of V600E and E542K showed that all samples with those mutations belonged to the right-sided colon cancer group. Conclusion: The suggested PCR-SERS method is multiplexed, flexible in probe design, easy to incorporate into existing PCR conditions, and was sensitive enough to detect mutations in blood plasma.


Outcomes and prognostic variables associated with central division hepatic lobectomies: 61 dogs.
To determine the outcome and prognostic variables associated with long-term survival and complications in dogs undergoing hepatic lobectomy of the central division. Multi-institutional retrospective case series. Sixty-one client-owned dogs with central division masses. Medical records of dogs undergoing hepatic lobectomy of the central division from January 1, 2000 to January 1, 2015 were reviewed for signalment, clinical signs, preoperative staging, preoperative cytology or biopsy results, date of procedure, location of mass, surgical technique, whether cholecystectomy or cholecystopexy was performed, complications, histopathologic diagnosis and margin evaluation, date of local recurrence or detection of metastatic disease, and survival. Hilar resection was associated with increased intraoperative and postoperative complications. Intraoperative complications occurred in 29 dogs, with 20 dogs experiencing intraoperative hemorrhage. Nineteen dogs required transfusions. Immediate postoperative complications occurred in 20 dogs. Perioperative mortality rate was 11%, and 2-week mortality rate was 14.7%. The median survival time for dogs with hepatocellular carcinoma (HCC) was not reached. The 1- and 3-year censored survival rates for dogs with HCC was 82.1% and 82.1%, respectively. Margin status did not impact survival time. Hepatic lobectomy of the central division was associated with hemorrhage in approximately 33% of dogs, but there was a relatively low perioperative mortality rate. Hepatic lobectomy for HCC resulted in long-term survival, regardless of margin status. Surgeons should anticipate the requirement for blood products in dogs that may require hepatic lobectomy of the central division. Long-term survival can be expected after surgical treatment of HCC, regardless of margin status.


Future strategies for treating erectile dysfunction.
Erectile dysfunction affects over half of all men between 50 and 70 years of age, and by the age of 40, about 40% of men may suffer from some form of erectile dysfunction. Many disease states, such as diabetes, hypertension, depression, and vascular disease, are associated with the condition, which may occur many years prior to the onset of these disorders. The phenomenal success of sildenafil in improving erections in men with erectile dysfunction is due to the fact that the drug, as a phosphodiesterase inhibitor, improves the relaxation of smooth muscle cells, which become dysfunctional with the aging process. However, not everyone responds to this medication, mainly because the efficacy of the drug is directly dependent on the release of nitric oxide from the nerve terminals of the cavernosal nerve, and this may become defective with aging/certain disease states. The goal of gene therapy for organic impotence is to allow the patient to sustain physiologically elicited erections without resorting to pharmacological treatment immediately prior to the sexual act. Experimental efforts in gene therapy for erectile dysfunction are likely to continue intensively in a series of directions, some specific to the nature of the selected gene to be manipulated or the physiology of the corpora cavernosa itself, and others extrapolatable from the advancement of gene therapy in general.


Health Knowledge and Adherence as Predictors of Viral Burden and CD4+ T-Cell Count in Youth and Young Adults Living With HIV.
Health literacy influences HIV treatment for youth and, thus, is a research priority. We explored health knowledge and self-reported adherence, as indicators of health literacy, among youth living with HIV (YLWH) and the association between health literacy and health outcomes. A total of 102 YLWH ages 13-25 years participated in the study. Participants completed the Brief Estimate of Health Knowledge and Action-HIV Version; CD4 T-cell counts and viral loads were extracted from participant medical records. Participants had a moderate amount of HIV knowledge, and most reported taking their medications under most conditions. Decreasing action scores were statistically associated with an increased likelihood of having a detectable viral load. Health literacy is an important factor that should be addressed by practitioners working with YLWH. More research is needed to determine the best way to measure and improve health literacy.


Outcome Measures in Late-Life Depression.
The constructs and suggested measures listed here are recommended for inclusion in clinical treatment trials of late-life depression to optimize the return on the significant effort involved in these studies. The suggested measures have shown utility in studies documenting outcomes in depression studies; however the measures listed are by no means to be interpreted as exhaustive. The authors propose that consistent use of a broad set of outcome measures will assist clinicians and policymakers in the identification of appropriate treatments for older, depressed patients.


Acute paraquat poisoning with sinus bradycardia: A case report.
Paraquat (PQ) is a highly toxic herbicide, which not only leads to acute organ damage, but also to a variety of complications. Patients with severe PQ-induced poisoning may succumb to multiple organ failure involving the circulatory and respiratory systems. Although numerous studies have been performed investigating PQ poisoning, cases of extreme bradycardia caused by acute PQ-induced poisoning are rare. In the present case report, a 59-year-old male who ingested PQ was admitted to the Department of Poisoning and Occupational Disease at Qilu Hospital of Shandong University (Jinan, China) after three days. The patient received treatment known as the 'Qilu scheme', which was established in the Department of Poisoning and Occupational Disease. However, the heart rate of the patient remained low following the administration of conventional medicines, until thyroid tablets were administered. To the best of our knowledge, cases of bradycardia following PQ poisoning are rare.


Shared storybook reading with children at family risk of dyslexia.
Shared storybook reading is an important context for language learning and often constitutes young children's first encounter with the printed word. The quality of early shared reading interactions is a known predictor of language and reading development, but few studies have examined these interactions in children at family risk of dyslexia. This exploratory study describes the quality of shared storybook reading between mothers and their 3- to 4-year-old children at family risk of dyslexia (FR; n = 18) in comparison with dyads with no known risk (no-FR; n = 13). Mother-child interactions while sharing a familiar and an unfamiliar storybook were coded for type of extra-textual talk (meaning-related talk at the concrete and abstract levels; print-related talk) and affective quality. Maternal and child language and literacy skills were considered as potential correlates of shared reading quality. The linguistic and affective quality of shared reading was broadly comparable across FR and no-FR dyads, particularly when sharing a book they knew well, with large within-group variation. Mothers contributed more concrete meaning-related talk when introducing an unfamiliar book to their children; children contributed more extra-textual talk overall when sharing a familiar book. Maternal language, but not reading, skills were related to the linguistic quality of shared reading. The affective quality of reading interactions was rated more highly in dyads where mothers and children had stronger language skills. These results suggest that the quality of shared reading does not vary systematically as a function of children's risk of dyslexia but is related to maternal language skills. This finding needs to be replicated in a larger sample in order to better understand the risk and protective factors associated with dyslexia. What is already known about this topic The quality of extra-textual talk during shared reading between parents and preschoolers predicts later language and literacy outcomes in typically developing children.The affective quality of early shared reading predicts children's motivation to read independently in later childhood.Children at family risk of dyslexia are more likely than their peers with no family risk to have difficulty learning to read and may show weaknesses in oral language skills. What this paper adds The linguistic and affective quality of shared reading between mothers and preschool children is broadly similar when children are at family risk of dyslexia compared with no family risk.The type and quantity of extra-textual talk contributed by mothers and children appears to differ according to the familiarity of the storybook, but replication of the findings in a larger sample is required.The linguistic and affective quality of shared reading is related to maternal language skills. Implications for theory, policy or practice Shared storybook reading offers rich language learning opportunities for children at family risk of dyslexia.Maternal language skills may be an important determinant of the interactional quality of shared reading.The linguistic and affective quality of shared reading is not clearly associated with maternal reading difficulties.


[Conservative surgical treatment for large maxillary cysts. Some comments on technique (author's transl)].
Conservative surgical treatment for large maxillary cysts consists of releasing the cystic wall of the bony cavity without destroying the pulp of the teeth which have apices close to the operated cavity (unless the tooth is already dead). The vestibular approach is through one or two orifices and is as small in size as possible. This technique generally allows conservation of the vitality of the largest number of teeth and avoids postoperative collapse.


Maternal and Child's Thyroid Function and Child's Intellect and Scholastic Performance.
Maternal hypothyroidism and/or hypothyroxinemia have been associated with child's poor neuropsychological development, but the results have been inconsistent. The Northern Finland Birth Cohort 1986 included all expected births within a year (9362 women, 9479 children) from the two northernmost provinces of Finland. Maternal serum samples (n = 5791) were obtained in early pregnancy (M ± SD = 10.7 ± 2.8 weeks' gestation), and serum samples from their children were obtained at 16 years of age (n = 5829). All samples were analyzed for thyrotropin, free thyroxine (fT4), and thyroid peroxidase antibodies. The children's school performance was evaluated by their main teachers at eight years of age, as well as by the adolescents themselves at 16 years of age. Data on possible severe intellectual deficiency and mild cognitive limitation were collected from healthcare records and registries for all children. Logistic regression estimated the odds of poor school performance or severe intellectual deficiency/mild cognitive limitation associated with exposure to maternal thyroid dysfunction. The odds of poor school performance associated with the adolescents' own thyroid function at age 16 were also estimated. Results are presented as odds ratios (OR) with confidence intervals (CI), adjusted for maternal/family covariates and child's sex. Girls of mothers with subclinical hypothyroidism had more self-evaluated difficulties in mathematics than did girls of euthyroid mothers (OR 1.62 [CI 1.06-2.49]). Boys of hypothyroxinemic mothers repeated a school class more often than did boys of euthyroid mothers (OR 5.46 [CI 1.19-25.06]). Adolescents of hyperthyroid mothers had increased odds of poor self-evaluated performance in mathematics (OR 1.61 [CI 1.01-2.49]). Maternal thyroid dysfunction did not increase the odds of a child having severe intellectual deficiency/mild cognitive limitation. At 16 years of age, girls with hyperthyroidism by laboratory measurements had more difficulties in Finnish language (OR 2.82 [CI 1.42-5.61]) than did euthyroid girls. Boys with hypothyroxinemia by laboratory measurement had higher odds of having difficulties in Finnish and/or mathematics (OR 2.13 [CI 1.26-3.62]) than did euthyroid boys. Maternal thyroid dysfunction during early pregnancy was associated with poorer scholastic performance of the adolescent. Additionally, adolescents' own thyroid dysfunction was associated with difficulties in school performance assessed by self-evaluation.


Fungi associated with hair roots of Rhododendron lochiae (Ericaceae) in an Australian tropical cloud forest revealed by culturing and culture-independent molecular methods.
The culturable fungal assemblage associated with hair roots of Rhododendron lochiae (Ericaceae) from a tropical cloud forest in Queensland, Australia was investigated using rDNA internal transcribed spacer (ITS) restriction fragment length polymorphisms (RFLPs) and sequence analysis, and the abilities of the fungi to form ericoid mycorrhizas were tested. DNA was further extracted directly from hair roots and partial fungal ITS products compared with those from the cultured isolate assemblage using denaturing gradient gel electrophoresis (DGGE). A range of ericoid mycorrhizal and non-mycorrhizal fungi was identified using both approaches, with ericoid mycorrhizal fungi found to be taxonomically similar to those associated with Ericaceae in temperate habitats worldwide. Both approaches identified several unique fungi and, although most of the abundant RFLP types identified in the cultured fungal assemblage were also present in DGGE profiles of DNA extracted directly from roots, one the most commonly isolated RFLP types, a putative Xylariaceae taxon, was absent. The data suggest that a combination of culturing and culture-independent approaches may be more efficacious than either method individually.


186Re-etidronate in breast cancer patients with metastatic bone pain.
The aim of this study was to evaluate the efficacy of 186Re-1,1-hydroxyethylidene diphosphonate (etidronate) in breast cancer patients with painful bone metastases. Thirty patients with advanced breast cancer who had metastatic bone pain were treated with 186Re-etidronate using different dosages in a noncomparative, open-label study. Twenty-four patients were evaluated for efficacy (6 patients had incomplete datasets). Dosages varied from 1295 to 2960 MBq (35 to 80 mCi). Efficacy was evaluated according to the multidimensional pain model using a paper-and-pencil diary. The diary was kept twice daily for 8-10 wk (2 wk before through 6-8 wk after 186Re-etidronate treatment). Response was determined with a strict criteria, in which pain intensity (PI), medication index (MI) and daily activities (DA) were core determinants. Response was defined as: (a) Reduced PI > or = 5% while MI and DA were at least constant; or (b) Reduced PI <25% in combination with improvement of MI or DA > or = 25%, without worsening of either factor. Duration of response should always exceed a minimum of 2 wk. Fifty-eight percent (n = 14) of all patients reported a response. The maximum follow-up period was 8 wk. Duration of response ranged from 2 to 8 wk (mean 4 wk). Patients (14/24) not only experienced considerable pain reduction, but in 12 patients this was also accompanied by noteworthy reduction in MI (> or = 25%). No clear dose-response relationship was found. With strict pain assessment criteria, 186Re-etidronate showed a response of 58% in the palliative treatment of metastatic bone pain originating from breast cancer.


Prevalence of Staphylococcus aureus and Pseudomonas aeruginosa in indoor air flora of a district hospital, Mandya, Karnataka.
Two year (1998 and 1999) extensive survey was carried out in Mandya district hospital, Karnataka for a period of three years to monitor the prevalence of Staphylococcus aureus, Pseudomonas aeruginosa (S. aureus and Ps. aeruginosa) from the indoor air samples of operation theater labor room, children's ward, male and female general wards postoperative wards etc. A rotary air sampler loaded with manital salt and Pseudomonas selection agar media strips were used to collect the samples from various sites. The survivallence results revealed the prevalence of S. aureus and Ps. aeruginosa in almost all sampling sites, irrespective of season indicating their long-term survival and consequent threat to hospitalized patients as well the working employees.


Action pattern, specificity, lytic activities, and physiological role of five digestive beta-glucanases isolated from Periplaneta americana.
Three laminarinases (LAM, LIC 1, and LIC 2) and two cellulases (CEL 1 and CEL 2) were purified to homogeneity from Periplaneta americana midguts. These beta-glucanases are secreted by salivary glands, stabilized by calcium ions, and have pH optima around 6. LAM (46 kDa) is active only on laminarin, native or with oxidized ends, and so it is an endo-beta-1,3-glucanase (EC 18.104.22.168). It processively releases mainly glucose from laminarin and shows lytic activity on fungal cells. LIC 1 (25 kDa) is an endo-beta-1,3(4)-glucanase (EC 126.96.36.199.), because it cleaves internal bonds on both laminarin and lichenin. LIC 1 lyses fungal cells and apparently have high affinity for sequences of cellotetraoses linked by beta-1,3 links, releasing cellotetraose from lichenin. The reaction catalyzed by LIC 1 is not in rapid equilibrium, as suggested by activity-pH data. These data also showed that a group in LIC 1 with pK=4.9 is necessary for substrate binding. LIC 2 (23 kDa) seems to be similar to LIC 1. The laminarinases are inactivated by carbodiimide, suggesting the presence of a carboxyl group involved in catalysis. LAM and LIC 2 are inhibited by excess laminarin as substrate. CEL 1 (72 kDa) and CEL 2 (73 kDa) quickly decrease the molecular weight of lichenin used as substrate. Therefore, they are endo-beta-1,4-glucanases (EC 188.8.131.52). Both CEL 1 and CEL 2 are also active on crystalline cellulose. The specificities of P. americana beta-glucanases agree with the omnivorous detritus-feeding habit of this insect, as they are able to attack plant (CEL 1, CEL 2, LIC 1 and LIC 2) and fungal (LIC 1 and LAM) cell walls.


[Clinical and endocrinological studies of the puerperium in cows].
A total of 85 cows were used to study the clinical course of the involution processes in the genital tract following calving. According to the season of calving the animals were divided into two groups: 1st group consisting of 29 cows whose calving and puerperium had taken place during the spring/summer period; IInd group of 56 cows with which these processes were observed in the autumn/winter period. Seven cows of each group were subjected to endocrinologic studies for the evaluation of the pituitary gonadotropic hormones (FSH, and LH) in the blood plasma, applying Brown's method and Parlow's method, respectively. The following conclusions were drawn: 1. The intensity of the involution processes in the sexual apparatus of cows depends on the season. In the spring/summer period they usually last 34.3 days, and in the autumn and winter -- 37.5 days. 2. Fast involution of the uterus has been observed during the first two weeks after calving. This process is considerably delayed during the third week. 3. The yellow body regresses in the course of 14 days following calving. Up to the 35th day this has been established only im 3.5 per cent of the cows. Clinically, follicles in the ovaries are established as early as the 15th day after calving. 4. The FSH and LH level in the blood plasma during the first days after calving has been low -- 73.7 mg/% for FSH, and 7.04 mg/% for LH, both showing a rising trend. The peak values have been established between the 15th and 40th, and the 22nd and 28th day, respectively.


Efficacy and safety of the siRNA JNJ-73763989 and the capsid assembly modulator JNJ-56136379 (bersacapavir) with nucleos(t)ide analogues for the treatment of chronic hepatitis B virus infection (REEF-1): a multicentre, double-blind, active-controlled, randomised, phase 2b trial.
JNJ-73763989 (JNJ-3989), a small interfering RNA, targets all hepatitis B virus (HBV) RNAs, reducing all HBV proteins. JNJ-56136379 (JNJ-6379; also known as bersacapavir), a capsid assembly modulator, inhibits HBV replication. We aimed to evaluate the efficacy (ie, antiviral activity) and safety of these therapeutics in combination with nucleos(t)ide analogues in patients with chronic hepatitis B. The REEF-1 multicentre, double-blind, active-controlled, randomised, phase 2b study was done at 108 hospitals or outpatient centres across 19 countries in Asia, Europe, and North and South America. We included patients aged 18-65 years with chronic hepatitis B (defined as HBsAg positivity at screening and at least 6 months before screening or alternative markers of chronicity [eg, HBV DNA]), including those not currently treated, virologically suppressed, HBeAg positive, and HBeAg negative. Patients were randomly assigned (1:1:2:2:2:2) via permuted block randomisation according to a computer-generated schedule to receive oral nucleos(t)ide analogues once per day plus placebo (control group); oral JNJ-6379 250 mg daily plus nucleos(t)ide analogues (JNJ-6379 dual group); nucleos(t)ide analogues plus subcutaneously injected JNJ-3989 at doses of 40 mg (JNJ-3989 dual 40 mg group), 100 mg (JNJ-3989 dual 100 mg group), or 200 mg (JNJ-3989 dual 200 mg group) every 4 weeks; or JNJ-6379 250 mg plus JNJ-3989 100 mg every 4 weeks plus nucleos(t)ide analogues (triple group) for 48 weeks followed by a follow-up phase. An interactive web response system provided concealed treatment allocation, and investigators remained masked to the intervention groups until the primary analysis at week 48. The primary endpoint was the proportion of patients meeting predefined nucleos(t)ide analogue-stopping criteria (alanine aminotransferase <3 × upper limit of normal, HBV DNA below the lower limit of quantitation, HBeAg negative, and HBsAg <10 IU/mL) at week 48. All patients who received at least one dose of study drug were included in the analysis population used for primary efficacy assessment, excluding those who withdrew because of COVID-19-related reasons, withdrew before week 44, or had no efficacy data (ie, the modified intention-to-treat population). Safety was assessed in all participants who received at least one dose of study drugs. This trial is registered with ClinicalTrials.gov, NCT03982186. The study has been completed. Between Aug 1, 2019, and April 26, 2022, 470 patients (310 [66%] male and 244 [52%] White) were randomly assigned: 45 to the control group, 48 to the JNJ-6379 dual group, 93 to the JNJ-3989 dual 40 mg group, 93 to the JNJ-3989 dual 100 mg group, 96 to the JNJ-3989 dual 200 mg group, and 95 to the triple group. At week 48, five (5%; 90% CI 2-11) of 91 patients in the JNJ-3989 dual 40 mg group, 15 (16%; 10-24) of 92 in the JNJ-3989 dual 100 mg group, 18 (19%; 13-27) of 94 in the JNJ-3989 dual 200 mg group, eight (9%; 4-15) of 94 in the triple group, and one (2%; 0-10) of 45 in the control group met nucleos(t)ide analogue stopping criteria. No patients in the JNJ-6379 dual group met stopping criteria. 38 (81%) patients who met nucleos(t)ide analogue-stopping criteria at week 48 were virologically suppressed and HBeAg negative at baseline. Ten (2%) of 470 patients had serious adverse events during the treatment phase, and two patients (one each from the JNJ-3989 dual 200 mg group [exercise-related rhabdomyolysis] and the triple group [increase in ALT or AST]) had serious adverse events related to study treatment. During follow-up, 12 (3%) of 460 patients had a serious adverse event; one (<1%), a gastric ulcer, was considered to be related to nucleos(t)ide analogues and occurred in a patient from the JNJ-3989 dual 200 mg group. 29 (6%) of 460 patients in the treatment phase and in ten (2%) of 460 patients in the follow-up phase had grade 3 or 4 adverse events. Five (1%) of 470 patients discontinued treatment due to adverse events, and there were no deaths. Although treatment with JNJ-3989 led to a dose-dependent response for meeting nucleos(t)ide analogue-stopping criteria, it rarely led to HBsAg seroclearance. However, most patients treated with JNJ-3989 had clinically meaningful reductions in HBsAg that might contribute to a liver environment conducive to better immune control and, in turn, might improve the response to immune-modulating therapies. Janssen Research and Development.


In Defense of P Values.
P values have become the scapegoat for a wide variety of problems in science. P values are generally over-emphasized, often incorrectly applied, and in some cases even abused. However, alternative methods of hypothesis testing will likely fall victim to the same criticisms currently leveled at P values if more fundamental changes are not made in the research process. Increasing the general level of statistical literacy and enhancing training in statistical methods provide a potential avenue for identifying, correcting, and preventing erroneous conclusions from entering the academic literature and for improving the general quality of patient care.


Inflammation and Cell Death During Cholestasis: The Evolving Role of Bile Acids.
Cholestasis results in blockage of bile flow whether the point of obstruction occurs extrahepatically or intrahepatically. Bile acids are a primary constituent of bile, and thus one of the primary outcomes is acute retention of bile acids in hepatocytes. Bile acids are normally secreted into the biliary tracts and then released into the small bowel before recirculating back to the liver. Retention of bile acids has long been hypothesized to be a primary cause of the associated liver injury that occurs during acute or chronic cholestasis. Despite this, a surge of papers in the last decade have reported a primary role for inflammation in the pathophysiology of cholestatic liver injury. Furthermore, it has increasingly been recognized that both the constituency of individual bile acids that make up the greater pool, as well as their conjugation status, is intimately involved in their toxicity, and this varies between species. Finally, the role of bile acids in drug-induced cholestatic liver injury remains an area of increasing interest. The purpose of this review is to critically evaluate current proposed mechanisms of cholestatic liver injury, with a focus on the evolving role of bile acids in cell death and inflammation.


Single-spin readout in a double quantum dot including a micromagnet.
We use photon-assisted tunneling (PAT) and an inhomogeneous Zeeman field to demonstrate spin-selective PAT readout with a double quantum dot. The inhomogeneous Zeeman field is generated by a proximal micromagnet, which provides different stray fields between the two dots, resulting in an energy difference between the interdot PAT of the up-spin state and that of the down-spin state. We apply various external magnetic fields to modify the relative filling weight between the up-spin and down-spin states and detect it by using a charge detection technique to probe the PAT induced charge delocalization in the double dot.


Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling.
Ischaemia-reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI-induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R-induced acute renal dysfunction and largely blunted I/R-induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL-positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro-apoptotic alteration of Bcl2/Bax expression, caspase-3 activation, loss of mitochondrial membrane potential and KATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the KATP channel blocker 5-HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post-I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage-associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL-1α, IL-6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1-mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI-induced AKI.


Primary bladder neck obstruction in men and women.
Primary bladder neck obstruction (PBNO) is a condition in which the bladder neck does not open appropriately or completely during voiding. Although the true prevalence of PBNO is difficult to ascertain, studies in both men and women with voiding dysfunction demonstrate a marked prevalence of the condition. Symptoms caused by PBNO include storage symptoms (frequency, urgency, urge incontinence, nocturia) and voiding symptoms (decreased force of stream, hesitancy, incomplete emptying). There are multiple theories as to the etiology of PBNO, including muscular and neurologic dysfunction and fibrosis. The diagnosis of PBNO can be made precisely with videourodynamics, urodynamic testing with simultaneous pressure-flow measurement, and visualization of the bladder neck during voiding. Treatments vary from watchful waiting to medical therapy to surgery, depending on the severity of symptoms, urodynamic findings, and response to therapy. This article reviews the current state of the art with respect to the prevalence, etiology, diagnosis, and treatment of PBNO.